Prevention and amelioration of skin symptoms such as age spots, freckles, and pigmentation, which are caused by factors such as increasing age, stress, and ultraviolet rays, are very important concerns especially for women.
In order to respond to such concerns, a variety of skin-whitening agents have been developed heretofore. For example, skin-whitening agents each including ascorbates, hydrogen peroxide, colloidal sulfur, glutathione, hydroquinone, or catechol have been developed (for example, see Non Patent Document 1 and Non Patent Document 2).
However, it is known that any of the skin-whitening agents are not effective for some symptoms. However, the reasons are not known in detail. Further, some of the skin-whitening agents are shown to have safety problems.
In addition, miconazole and clotrimazole, which are known as antimycotics, have been reported to have tyrosinase inhibitory activities (Patent Documents 2 and 3). However, miconazole and clotrimazole each have a high antimycotic activity, and hence it is problematic in safety to use the compounds in an external preparation for skin such as a cosmetic.
In this context, development of a novel skin-whitening agent which has an excellent skin-whitening effect and is highly safe has been desired.
On the other hand, a sterically-bulky aromatic group (in particular, a diphenylmethyl group or a triphenylmethyl group) or an aromatic heterocyclic group is widely known as an effective protective group for a hydroxyl group or an amino group in synthesis of an organic low-molecular-weight compound, a peptide, and a nucleic acid (for example, see Non Patent Document 3 and Non Patent Document 4). An intermediate compound obtained by using such protective group (for example, see Non Patent Document 5 and Non Patent Document 6) is applied to organic syntheses on a wide range of scales from a laboratory scale to an industrial scale.
Further, it has been reported that some of compounds each having a chemical structure including a sterically-bulky substituent such as a substituted diphenylmethyl group or triphenylmethyl group have biological activities such as an antitumor activity (for example, see Non Patent Document 5), an antimycotic effect (for example, see Patent Document 1), an antihistaminic effect (for example, see Non Patent Document 6), a dopamine uptake inhibitory effect (for example, see Non Patent Document 7), and a calcium antagonistic effect (for example, see Non Patent Document 8).    [Patent Document 1] JP 09-255634 A    [Patent Document 2] WO 02/060404 A1    [Patent Document 3] KR 10-2004-0007044 A    [Non Patent Document 1] Edited by Katsuyuki Takeda et. al., “Utility, Evaluation Technology and Future Perspective of Cosmetics”, published by YAKUJI NIPPO LIMITED. (2001)    [Non Patent Document 2] Yoshiyuki Ohmori, FRAGRANCE JOURNAL, extra edition, No. 14, 1995, 118-126    [Non Patent Document 3] Theodora W. Green, Protective Groups in Organic Synthesis, A Wiley-Interscience Publication.: 1981, P 173-176 and P 273-274    [Non Patent Document 4] Nobuo Izumiya, Tetsuo Kato, Haruhiko Aoyagi, Michinori Waki, Basic and Experiment of Peptide Synthesis: MARUZEN Co., Ltd., 1985, P 38    [Non Patent Document 5] Naohisa Ogo et. al., Bioorganic & Medicinal Chemistry, 17(14), 3921-3924 (2007)    [Non Patent Document 6] Sasse A., et. al., Bioorganic & Medicinal Chemistry, 8(5), 1139-1149 (2000)    [Non Patent Document 7] Dutta A K. et. al., Bioorganic & Medicinal Chemistry, 11(17), 2337-2340 (2001)    [Non Patent Document 8] Shanklin J R Jr., et al., J. Med. Chem., 34(10), 3011-3022 (1991)